CONTRIBUTION OF ENDOTHELIUM-DERIVED RELAXING FACTOR TO EXERCISE-INDUCED VASODILATION IN HUMANS

Release of endothelium-derived relaxing factor (EDRF) from the vascular endothelium may contribute to skeletal muscle arteriolar vasodilation during exercise. The present study was undertaken to test this hypothesis. Ten normal subjects underwent brachial arterial catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow was then measured at rest, during two levels of wrist flexion exercise (0.2 and 0.4 W), and during 0.4-W exercise with concurrent infusion of norepinephrine (100 ng.min(-1) 100 ml forearm volume(-1)). Measurements were made with and without infusion of N-monomethyl-L-arginine (L-NMMA) (0.1-0.2 mg.min(-1) 100 ml forearm volume(-1)), a specific inhibitor of EDRF synthesis. Infusion of L-NMMA reduced resting forearm blood flow (control: 2.5 +/- 0.4 vs. L-NMMA: 1.5 +/- 0.1 ml.min(-1) 100 ml(-1)) and markedly reduced forearm blood flow response to acetylcholine (5 mu g.min(-1) 100 ml(-1) forearm volume(-1)) (control: 20.2 +/- 2.9 vs. L-NMMA: 4.0 +/- 1.0 ml.min-1.100 ml-1; both P < 0.01). However, L-NMMA has no significant effect on flow responses to exercise (0.2 W:8.3 +/- 1.1 vs. 8.3 +/- 1.2; 0.4 W: 13.8 +/- 1.7 vs. 13.5 +/- 1.7; 0.4 W + norepinephrine: 10.3 +/- 2.4 vs. 9.4 +/- 2.6 ml.min(-1).100 ml(-1), all P=NS). These findings suggest that release of EDRF from the vascular endothelium contributes to skeletal muscle arteriolar vasodilation produced by exercise.